Roche steers Gazy­va in­to a new PhI­II pro­gram af­ter com­bo shows promise in lu­pus nephri­tis study

Roche is work­ing on putting to­geth­er a late-stage study for its mon­o­clon­al an­ti­body Gazy­va in pa­tients with se­vere kid­ney dis­ease as­so­ci­at­ed with lu­pus af­ter a com­bi­na­tion ap­proach helped pa­tients in a mid-stage study.

The 125-pa­tient NO­BIL­I­TY tri­al eval­u­at­ed Gazy­va, com­bined with stan­dard-of-care treat­ment my­cophe­no­late mofetil or my­cophe­no­lic acid and cor­ti­cos­teroids, ver­sus stan­dard treat­ment alone. The com­bo met the main goal of in­duc­ing a sta­tis­ti­cal­ly su­pe­ri­or com­plete re­nal re­sponse (CRR) of 40% at week 76, ver­sus 18% in pa­tients giv­en stan­dard treat­ment, Roche said.

The drug, which is be­ing test­ed alone and in com­bi­na­tion with oth­er ther­a­pies across a range of blood can­cers, is en­gi­neered to at­tach to CD20, a pro­tein found on cer­tain B-cells. It is thought to work by at­tack­ing tar­get­ed cells both di­rect­ly and in tan­dem with the body’s im­mune sys­tem. Gazy­va, which is al­ready ap­proved for use in cer­tain can­cers, gen­er­at­ed near­ly $342 mil­lion in the first nine months of 2019 and has been grant­ed break­through ther­a­py sta­tus for lu­pus nephri­tis.

On the safe­ty side, wor­ries that pro­found B cell de­ple­tion would ham­per the drug’s pro­file were abat­ed af­ter the Gazy­va arm reg­is­tered a se­ri­ous ad­verse event rate of 24%, while pa­tients on the stan­dard care arm saw a rate of 29%. In terms of se­ri­ous in­fec­tions, the rate was 9% on the Gazy­va arm and 18% in the stan­dard group.

Richard Fu­rie North­well Health

“The strat­e­gy to tar­get B cells (an­ti­body-pro­duc­ing white blood cells re­spon­si­ble for pro­duc­ing lu­pus an­ti­bod­ies) in sys­temic lu­pus and lu­pus nephri­tis was bi­o­log­i­cal­ly sound. How­ev­er, two stud­ies did not achieve their re­spec­tive end­points,” said Richard Fu­rie, chief of rheuma­tol­ogy at North­well Health in a state­ment.

“Af­ter a hia­tus of sev­er­al years, a de­ci­sion was made to move for­ward with a third-gen­er­a­tion B cell-de­plet­ing an­ti­body…The hy­poth­e­sis was that a more po­tent an­ti­body might re­sult in greater de­ple­tion of B cells and that this may yield a greater clin­i­cal re­sponse in those pa­tients with ac­tive kid­ney dis­ease.”

Lu­pus is a drug de­vel­op­er’s night­mare. In the last six decades, there has been one FDA ap­proval. In re­cent years, the field has re­sem­bled a grave­yard. Last Oc­to­ber, UCB and Bio­gen’s $BI­IB an­ti-CD40L drug failed in a late-stage study, months af­ter Xen­cor $XN­CR and Sanofi’s $SNY Abl­ynx al­so con­ced­ed de­feat in their pro­grams. In Au­gust, how­ev­er, As­traZeneca of­fered a glim­mer of hope af­ter its drug, an­i­frol­um­ab, cleared a Phase III study.

The on­ly bi­o­log­ic so far to win ap­proval for lu­pus is GSK’s $GSK Benlysta — which was cleared for adult use in 2011 and for rare cas­es of child­hood lu­pus this year. (GSK is in the midst of test­ing Benlysta in com­bi­na­tion with Roche’s rit­ux­imab in the hope the com­bi­na­tion will have a more po­tent ef­fect on the dis­ease ver­sus Benlysta monother­a­py.)

The sys­temic au­toim­mune dis­ease, in which the body’s im­mune sys­tem launch­es an at­tack on its own tis­sues and or­gans, af­fects about 1.5 mil­lion Amer­i­cans, ac­cord­ing to The Lu­pus Foun­da­tion of Amer­i­ca. Lu­pus nephri­tis oc­curs when the dis­ease rav­ages the kid­neys, trig­ger­ing in­flam­ma­tion that could lead to blood and/or pro­tein in the urine, high blood pres­sure, poor kid­ney func­tion, or kid­ney fail­ure. Rough­ly 60% of lu­pus pa­tients de­vel­op lu­pus nephri­tis and 1 in 4 progress to end-stage re­nal dis­ease.

So­cial im­age: Roche

UP­DAT­ED: Bio­gen shares spike as ex­ecs com­plete a de­layed pitch for their con­tro­ver­sial Alzheimer's drug — the next move be­longs to the FDA

Biogen is stepping out onto the high wire today, reporting that the team working on the controversial Alzheimer’s drug aducanumab has now completed their submission to the FDA. And they want the agency to bless it with a priority review that would cut the agency’s decision-making time to a mere 6 months.

The news drove a 10% spike in Biogen’s stock $BIIB ahead of the bell.

Part of that spike can be attributed to a relief rally. Biogen execs rattled backers and a host of analysts earlier in the year when they unexpectedly delayed their filing to the third quarter. That delay provoked all manner of speculation after CEO Michel Vounatsos and R&D chief Al Sandrock failed to persuade influential observers that the pandemic and other factors had slowed the timeline for filing. Actually making the pitch at least satisfies skeptics that the FDA was not likely pushing back as Biogen was pushing in. From the start, Biogen execs claimed that they were doing everything in cooperation with the FDA, saying that regulators had signaled their interest in reviewing the submission.

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Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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Atul Deshpande, Harbour BioMed chief strategy officer & head, US operations (Harbour BioMedO

An­oth­er biotech IPO set-up? Multi­na­tion­al biotech leaps from round to round, scoop­ing up cash at a blis­ter­ing pace

A short four months after announcing a $75 million haul in Series B+ fundraising, the multinational biotech Harbour BioMed pulled in another round of investments and eclipsed the nine-digit mark in the process.

Harbour completed its Series C financing, the company announced Thursday morning, raising $102.8 million and bringing its total investment sum to over $300 million since its founding in late 2016. The biotech plans to use the money to transition early-stage candidates from the discovery phase, fund candidates already in the clinic, and prep late-stage candidates for commercialization.

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Ed Engleman (Stanford Blood Center)

Stan­ford star on­col­o­gy sci­en­tist Ed En­gle­man helped cre­ate the im­munother­a­py field. Now he wants to shake up neu­rode­gen­er­a­tion R&D

Over the last generation of drug R&D, Ed Engleman has been a standout scientist.

The Stanford professor co-founded Dendreon and provided the scientific insights needed to develop Provenge into a pioneering — though not particularly marketable — immunotherapy. He’s spurred a slate of startups, assisted by his well-connected perch as a co-founder of Vivo Capital, and took the dendritic cell story into its next chapter at a startup called Bolt.

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Nello Mainolfi (Kymera via YouTube)

Out to re­vive R&D, a resur­gent Sanofi pays $150M cash to part­ner up with a pi­o­neer­ing pro­tein degra­da­tion play­er

Frank Nestle was appointed Sanofi’s global head of immunology and inflammation research therapeutic area just days before dupilumab, the blockbuster-to-be IL-4 antibody, would be accepted for priority review. After four years of consolidating immunology expertise from multiple corners of the Sanofi family and recruiting new talents to build the discovery engine, he’s set eyes on a Phase I-ready program that he believes can grow into a Dupixent-sized franchise.

Covid-19 roundup: CDC de­bat­ing who should get first avail­able vac­cines; EU in Gilead talks af­ter US gob­bled first remde­sivir dos­es

The federal government has now spent billions of dollars accelerating the development of a Covid-19 vaccine, and yet they’ve remained hush-hush on who, precisely, would actually get inoculated once the first doses are approved and available. Internally, though, they have been debating it.

The CDC and an advisory committee of outside health experts have been working since April to devise a ranking system that would determine who receives a vaccine and when, The New York Times reported. The question of who is first in line for inoculation is important because no matter how many doses developers can make or how quickly they can make them, doses will still come out in batches; 300 million inoculations will not appear overnight.

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Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

A new study points to $6.5B in pub­lic sup­port build­ing the sci­en­tif­ic foun­da­tion of Gilead­'s remde­sivir. Should that be re­flect­ed in the price?

By drug R&D standards, Gilead’s move to repurpose remdesivir for Covid-19 and grab an emergency use authorization was a remarkably easy, low-cost layup that required modest efficacy and a clean safety profile from just a small group of patients.

The drug OK also arrived after Gilead had paid much of the freight on getting it positioned to move fast.

In a study by Fred Ledley, director of the Center for Integration of Science and Industry at Bentley University in Waltham, MA, researchers concluded that the NIH had invested only $46.5 million in the research devoted to the drug ahead of the pandemic, a small sum compared to the more than $1 billion Gilead expected to spend getting it out this year, all on top of what it had already cost in R&D expenses.

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Francis Collins, NIH director (Sean Zanni/Patrick McMullan via Getty Images)

NIH kicks off Covid-19 vac­cine, mon­o­clon­al an­ti­body re­search net­work

The NIH today announced the kickoff of a national clinical trials network to test vaccines and other treatments that could prevent infection with SARS-CoV-2, the virus that causes infection with Covid-19.

The network has been established by the National Institute of Allergy and Infectious Diseases (NIAID) through the merger of four previously existing clinical trials networks that focused on HIV/AIDS.

FDA bars the door — for now — against Mer­ck’s star can­cer drug af­ter Roche beat them to the punch

Merck has been handed a rare setback at the FDA.

After filing for the accelerated approval of a combination of their star PD-1 drug Keytruda with Eisai’s Lenvima as a first-line treatment for unresectable hepatocellular carcinoma, the FDA nixed the move, handing out a CRL because Roche beat them to the punch on the same indication by a matter of weeks.

According to Merck:

Ahead of the Prescription Drug User Fee Act action dates of Merck’s and Eisai’s applications, another combination therapy was approved based on a randomized, controlled trial that demonstrated overall survival. Consequently, the CRL stated that Merck’s and Eisai’s applications do not provide evidence that Keytruda in combination with Lenvima represents a meaningful advantage over available therapies for the treatment of unresectable or metastatic HCC with no prior systemic therapy for advanced disease. Since the applications for KEYNOTE-524/Study 116 no longer meet the criteria for accelerated approval, both companies plan to work with the FDA to take appropriate next steps, which include conducting a well-controlled clinical trial that demonstrates substantial evidence of effectiveness and the clinical benefit of the combination.

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